Abstract Title:

Melatonin prevents the Drp1-dependent mitochondrial fission and oxidative insult in the cortical neurons after MPP(+) treatment.

Abstract Source:

J Pineal Res. 2016 May 9. Epub 2016 May 9. PMID: 27159033

Abstract Author(s):

Jih-Ing Chuang, I-Ling Pan, Chia-Yun Hsieh, Chiu-Ying Huang, Pei-Chun Chen, Jyh Wei Shin

Article Affiliation:

Jih-Ing Chuang


Mitochondrial dysfunction and oxidative stress are involved in the pathogenesis of Parkinson's disease (PD). Mitochondrial morphology is dynamic and precisely regulated by the mitochondrial fission and fusion machinery. Aberrant mitochondrial fragmentation controlled by the mitochondrial fission protein, dynamin-related protein 1 (Drp1) may result in cell death. Our previous results showed that melatonin protected neurons by inhibiting oxidative stress in a 1-methyl-4-phenylpyridinium (MPP(+) )-induced PD model. However, the effect of melatonin on mitochondrial dynamics remains uncharacterized. Herein, we investigated the effect of melatonin and the role of Drp1 on MPP(+) -induced mitochondrial fission in rat primary cortical neurons. We found that MPP(+) induced a rapid increase in the ratio of GSSG:total glutathione (a marker of oxidative stress) and mitochondrial fragmentation, Drp1 upregulation within 4 h, and finally resulted in neuron loss 48 h after the treatment. Neurons overexpressing wild type Drp1 promoted mitochondrial and nuclear fragmentation; however, neurons overexpressing dominant negative Drp1(K38A) or co-treated with melatonin exhibited significantly reduced MPP(+) -induced mitochondrial fragmentation and neuron death. Moreover, melatonin co-treatment prevented an MPP(+) -induced high ratio of GSSG and mitochondrial Drp1 upregulation. The prevention of mitochondrial fission by melatonin was not found in neurons transfected with wild type Drp1. These results provide a new insight that the neuroprotective effect of melatonin against MPP(+) toxicity is mediated by inhibiting the oxidative stress and Drp1-mediated mitochondrial fragmentation. This article is protected by copyright. All rights reserved.

Study Type : In Vitro Study

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